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Emerging Role of Fluciclovine and Other Next Generation PET Imaging Agents in Prostate Cancer Management

  • NUCLEAR MEDICINE & PET/CT IMAGING (R FLAVELL, SECTION EDITOR)
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Abstract

Purpose of Review

Prostate cancer recurrence after definitive therapy is not uncommon. Recurrent disease is first detected by the elevation of prostate specific antigen (PSA) and may often be radiographically occult. The use of molecular imaging for the localization and staging of recurrent prostate cancer is promising. 18F-Fluciclovine is a synthetic amino acid analog positron emission tomography (PET) tracer which has demonstrated great utility in the evaluation of patients with suspected recurrence disease. Other newer PET tracers such 68Ga/18F-PSMA-ligands are being investigated for prostate imaging with promising results. The purpose of this article is to review the emerging role of fluciclovine in clinical practice for patients with prostate cancer.

Recent Findings

Since the approval of fluciclovine by the Food and Drug Administration, the modality is widely used in the USA for patients with suspect disease recurrence. With the coming approval of newer generation of PET tracers, it is important to understand the unique mechanism of action and the diagnostic performance of fluciclovine PET/CT in prostate cancer imaging to allow better allocation of the radiotracers.

Summary

This review article provides a broad literature review of the current and the future potential role of fluciclovine PET/CT in prostate cancer imaging.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Information, A.C.S.M. Key statistics for prostate cancer. 5 Jan 2017;. Accessed 16 Feb 2016. https://www.cancer.org/cancer/prostate-cancer/about/key-statistics.html.

  2. Cookson MS, et al. Variation in the definition of biochemical recurrence in patients treated for localized prostate cancer: the American Urological Association Prostate Guidelines for Localized Prostate Cancer Update Panel report and recommendations for a standard in the reporting of surgical outcomes. J Urol. 2007;177(2):540–5.

    Article  CAS  PubMed  Google Scholar 

  3. Gleason, D.F. and G.T. Mellinger, Prediction of prognosis for prostatic adenocarcinoma by combined histological grading and clinical staging. 1974. J Urol, 2002. 167(2 Pt 2): p. 953-8; discussion 959.

  4. Schiavina R, et al. Diagnostic imaging work-up for disease relapse after radical treatment for prostate cancer: how to differentiate local from systemic disease? The urologist point of view. Rev Esp Med Nucl Imagen Mol. 2013;32(5):310–3.

    CAS  PubMed  Google Scholar 

  5. Turkbey B, et al. Imaging localized prostate cancer: current approaches and new developments. AJR Am J Roentgenol. 2009;192(6):1471–80.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Martarello L, et al. Synthesis of syn- and anti-1-amino-3-[18F]fluoromethyl-cyclobutane-1-carboxylic acid (FMACBC), potential PET ligands for tumor detection. J Med Chem. 2002;45(11):2250–9.

    Article  CAS  PubMed  Google Scholar 

  7. Nye JA, et al. Biodistribution and radiation dosimetry of the synthetic nonmetabolized amino acid analogue anti-18F-FACBC in humans. J Nucl Med. 2007;48(6):1017–20.

    Article  CAS  PubMed  Google Scholar 

  8. Oka S, et al. A preliminary study of anti-1-amino-3-18F-fluorocyclobutyl-1-carboxylic acid for the detection of prostate cancer. J Nucl Med. 2007;48(1):46–55.

    CAS  PubMed  Google Scholar 

  9. Schuster D, et al. Initial experience with the radiotracer anti-1-amino-3-F-18-fluorocyclobutane-1-carboxylic acid with PET/CT in prostate carcinoma. J Nucl Med. 2007;48(1):56–63.

    CAS  PubMed  Google Scholar 

  10. Blue Earth Diagnostics|U.S. FDA Approves Blue Earth Diagnostics’ AxuminTM (Fluciclovine F 18) Injection after Priority Review for PET Imaging of Recurrent Prostate Cancer—Blue Earth Diagnostics.

  11. Washburn LC, et al. Effect of structure on tumor specificity of alicyclic alpha-amino acids. Cancer Res. 1978;38(8):2271–3.

    CAS  PubMed  Google Scholar 

  12. Jager PL, et al. Radiolabeled amino acids: basic aspects and clinical applications in oncology. J Nucl Med. 2001;42(3):432–45.

    CAS  PubMed  Google Scholar 

  13. Oka S, et al. Transport mechanisms of trans-1-amino-3-fluoro[1-(14)C]cyclobutanecarboxylic acid in prostate cancer cells. Nucl Med Biol. 2012;39(1):109–19.

    Article  CAS  PubMed  Google Scholar 

  14. Goberdhan DCI, Wilson C, Harris AL. Amino acid sensing by mTORC1: intracellular transporters mark the spot. Cell Metab. 2016;23:580–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Xu M, et al. Up-regulation of LAT1 during antiandrogen therapy contributes to progression in prostate cancer cells. J Urol. 2016;195(5):1588–97.

    Article  PubMed  Google Scholar 

  16. Schuster DM, et al. Anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid: physiologic uptake patterns, incidental findings, and variants that may simulate disease. J Nucl Med. 2014;55(12):1986–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Bach-Gansmo T, et al. Multisite experience of the safety, detection rate and diagnostic performance of fluciclovine (18F) positron emission tomography/computerized tomography imaging in the staging of biochemically recurrent prostate cancer. J Urol. 2017;197(3 Pt 1):676–83.

    Article  PubMed  Google Scholar 

  18. Savir-Baruch B, et al. Diagnostic performance of synthetic amino acid anti-3-[18F] FACBC PET in recurrent prostate carcinoma utilizing single-time versus dual-time point criteria. J Nucl Med. 2014;55(supplement 1):21.

    Google Scholar 

  19. Litwin MS, Tan HJ. The diagnosis and treatment of prostate cancer: a review. JAMA. 2017;317(24):2532–42.

    Article  PubMed  Google Scholar 

  20. Scheenen TW, et al. Multiparametric magnetic resonance imaging in prostate cancer management: current status and future perspectives. Invest Radiol. 2015;50(9):594–600.

    Article  CAS  PubMed  Google Scholar 

  21. Kurhanewicz J, et al. Multiparametric magnetic resonance imaging in prostate cancer: present and future. Curr Opin Urol. 2008;18(1):71–7.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Beyersdorff D, et al. Patients with a history of elevated prostate-specific antigen levels and negative transrectal US-guided quadrant or sextant biopsy results: value of MR imaging. Radiology. 2002;224(3):701–6.

    Article  PubMed  Google Scholar 

  23. Barentsz JO, et al. ESUR prostate MR guidelines 2012. Eur Radiol. 2012;22(4):746–57.

    Article  PubMed  PubMed Central  Google Scholar 

  24. De Visschere PJ, et al. Role of multiparametric magnetic resonance imaging in early detection of prostate cancer. Insights Imaging. 2016;7(2):205–14.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Barentsz JO, et al. Synopsis of the PI-RADS v2 guidelines for multiparametric prostate magnetic resonance imaging and recommendations for use. Eur Urol. 2016;69(1):41–9.

    Article  PubMed  Google Scholar 

  26. Fei B, et al. PET-directed, 3D ultrasound-guided prostate biopsy. Diagn Imaging Eur. 2013;29(1):12–5.

    PubMed  PubMed Central  Google Scholar 

  27. •• Turkbey B, et al. Localized prostate cancer detection with 18F FACBC PET/CT: comparison with MR imaging and histopathologic analysis. Radiology. 2014;270(3):849–56. A prospective study demonstrating the limitation of fluciclovine PET/CT scan in the evaluation of patients with primary prostate cancer.

    Article  PubMed  Google Scholar 

  28. Schuster DM, et al. Characterization of primary prostate carcinoma by anti-1-amino-2-[(18)F] -fluorocyclobutane-1-carboxylic acid (anti-3-[(18)F] FACBC) uptake. Am J Nucl Med Mol Imaging. 2013;3(1):85–96.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Elschot M, et al. Combined (18)F-fluciclovine PET/MRI shows potential for detection and characterization of high-risk prostate cancer. J Nucl Med. 2018;59(5):762–8.

    Article  CAS  PubMed  Google Scholar 

  30. Jambor I, et al. Prospective evaluation of (18)F-FACBC PET/CT and PET/MRI versus multiparametric MRI in intermediate- to high-risk prostate cancer patients (FLUCIPRO trial). Eur J Nucl Med Mol Imaging. 2018;45(3):355–64.

    Article  PubMed  Google Scholar 

  31. De Visschere P, et al. Clinical and imaging tools in the early diagnosis of prostate cancer, a review. Jbr-btr. 2010;93(2):62–70.

    PubMed  Google Scholar 

  32. Rabbani F, et al. Incidence and clinical significance of false-negative sextant prostate biopsies. J Urol. 1998;159(4):1247–50.

    Article  CAS  PubMed  Google Scholar 

  33. Andriole GL, et al. Is there a better way to biopsy the prostate? Prospects for a novel transrectal systematic biopsy approach. Urology. 2007;70(6 Suppl):22–6.

    Article  PubMed  Google Scholar 

  34. Hara R, et al. Optimal approach for prostate cancer detection as initial biopsy: prospective randomized study comparing transperineal versus transrectal systematic 12-core biopsy. Urology. 2008;71(2):191–5.

    Article  PubMed  Google Scholar 

  35. Hambrock T, et al. Prospective assessment of prostate cancer aggressiveness using 3-T diffusion-weighted magnetic resonance imaging-guided biopsies versus a systematic 10-core transrectal ultrasound prostate biopsy cohort. Eur Urol. 2012;61(1):177–84.

    Article  PubMed  Google Scholar 

  36. Logan JK, et al. Current status of magnetic resonance imaging (MRI) and ultrasonography fusion software platforms for guidance of prostate biopsies. BJU Int. 2014;114(5):641–52.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Schuster DM, et al. Detection of recurrent prostate carcinoma with anti-1-amino-3-18F-fluorocyclobutane-1-carboxylic acid PET/CT and 111In-capromab pendetide SPECT/CT. Radiology. 2011;259(3):852–61.

    Article  PubMed  PubMed Central  Google Scholar 

  38. •• Schuster DM, et al. Anti-3-[(18)F]FACBC positron emission tomography-computerized tomography and (111)In-capromab pendetide single photon emission computerized tomography-computerized tomography for recurrent prostate carcinoma: results of a prospective clinical trial. J Urol. 2014;191(5):1446–53. The diagnostic performance of fluciclovine PET/CT scan in patients with suspected prostate cancer recurrence.

  39. Savir-Baruch B, et al. Anti-FACBC uptake pattern in the prostate affects positive predictive value and is associated with the presence of brachytherapy seeds. J Nucl Med. 2013;54(2_MeetingAbstracts):346.

    Google Scholar 

  40. Odewole OA, et al. Recurrent prostate cancer detection with anti-3-[18F]FACBC PET/CT: comparison with CT. Eur J Nucl Med Mol Imaging. 2016;43(10):177.

    Article  CAS  Google Scholar 

  41. Calabria F, et al. PET/CT with 18F-choline: physiological whole bio-distribution in male and female subjects and diagnostic pitfalls on 1000 prostate cancer patients. Nucl Med Biol. 2017;51:40–54.

    Article  CAS  PubMed  Google Scholar 

  42. Fanti S, et al. PET/CT with (11)C-choline for evaluation of prostate cancer patients with biochemical recurrence: meta-analysis and critical review of available data. Eur J Nucl Med Mol Imaging. 2016;43(1):55–69.

    Article  CAS  PubMed  Google Scholar 

  43. • Nanni C, et al. F-FACBC (anti1-amino-3-F-fluorocyclobutane-1-carboxylic acid) versus C-choline PET/CT in prostate cancer relapse: results of a prospective trial. Eur J Nucl Med Mol Imaging. 2016;43(9):1601–10. The comparison of Choline to fluciclovine. An intrapatient analysis.

  44. Perera M, et al. Sensitivity, specificity, and predictors of positive (68)Ga-prostate-specific membrane antigen positron emission tomography in advanced prostate cancer: a systematic review and meta-analysis. Eur Urol. 2016;70(6):926–37.

    Article  PubMed  Google Scholar 

  45. Fendler W, et al. Accuracy of 68Ga-PSMA11 PET/CT on recurrent prostate cancer: preliminary results from a phase 2/3 prospective trial. J Clin Oncol. 2018;36(15):5001.

    Article  Google Scholar 

  46. Afshar-Oromieh A, et al. Diagnostic performance of 68Ga-PSMA-11 (HBED-CC) PET/CT in patients with recurrent prostate cancer: evaluation in 1007 patients. Eur J Nucl Med Mol Imaging. 2017;44(8):1258–68.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Afshar-Oromieh A, et al. Comparison of PET imaging with a (68)Ga-labelled PSMA ligand and (18)F-choline-based PET/CT for the diagnosis of recurrent prostate cancer. Eur J Nucl Med Mol Imaging. 2014;41(1):11–20.

    Article  CAS  PubMed  Google Scholar 

  48. Savir-Baruch B, Zanoni L, Schuster DM. Imaging of prostate cancer using fluciclovine. PET Clin. 2017;12(2):145–57.

    Article  PubMed  Google Scholar 

  49. • Savir-Baruch B, et al. ACR-ACNM practice parameter for the performance of fluorine-18 fluciclovine-PET/CT for recurrent prostate cancer. Clin Nucl Med. 2018;43(12):909–17. The ACR practice parameters for the performance of fluciclovine PET/CT.

  50. Miller MP, et al. Reader training for the restaging of biochemically recurrent prostate cancer using (18)F-fluciclovine PET/CT. J Nucl Med. 2017;58(10):1596–602.

    Article  CAS  PubMed  Google Scholar 

  51. Lovrec P, et al. Factors influencing the positivity rate of commercial 18F-Fluciclovine imaging in men with suspected recurrent prostate cancer. J Nucl Med. 2018;59(supplement 1):1470.

    Google Scholar 

  52. Okotie OT, et al. Predictors of metastatic disease in men with biochemical failure following radical prostatectomy. J Urol. 2004;171(6 Pt 1):2260–4.

    Article  PubMed  Google Scholar 

  53. Offermann A, et al. Prognostic value of the new prostate cancer international society of urological pathology grade groups. Front Med. 2017;4:157.

    Article  Google Scholar 

  54. Montironi R, et al. Prostate carcinoma II: prognostic factors in prostate needle biopsies. BJU Int. 2006;97(3):492–7.

    Article  PubMed  Google Scholar 

  55. Howard LE, et al. Thresholds for PSA doubling time in men with non-metastatic castration-resistant prostate cancer. BJU Int. 2017;120(5b):E80–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Epstein JI, et al. The 2014 International Society of Urological Pathology (ISUP) consensus conference on gleason grading of prostatic carcinoma: definition of grading patterns and proposal for a new grading system. Am J Surg Pathol. 2016;40(2):244–52.

    PubMed  Google Scholar 

  57. Lovec P, et al. Positive findings on 18F-fluciclovine PET/CT in patients with suspected recurrent prostate cancer and PSA levels < 0.5 and < 0.3 ng/ml. Int J Radiat Oncol Biol Phys. 2018;102(3):161.

    Article  Google Scholar 

  58. England JR, et al. 18F-Fluciclovine PET/CT detection of recurrent prostate carcinoma in patients with serum PSA </= 1 ng/mL after definitive primary treatment. Clin Nucl Med. 2019;44(3):e128–32.

    Article  PubMed  Google Scholar 

  59. Loeb S, et al. Evaluation of the 2015 Gleason Grade Groups in a Nationwide Population-based Cohort. Eur Urol. 2016;69(6):1135–41.

    Article  PubMed  Google Scholar 

  60. Makarov DV, et al. Updated nomogram to predict pathologic stage of prostate cancer given prostate-specific antigen level, clinical stage, and biopsy Gleason score (Partin tables) based on cases from 2000 to 2005. Urology. 2007;69(6):1095–101.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Trock BJ, et al. Prostate cancer-specific survival following salvage radiotherapy vs observation in men with biochemical recurrence after radical prostatectomy. JAMA. 2008;299(23):2760–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Stephenson AJ, et al. Salvage radiotherapy for recurrent prostate cancer after radical prostatectomy. JAMA. 2004;291(11):1325–32.

    Article  CAS  PubMed  Google Scholar 

  63. Nguyen PL, et al. Patient selection, cancer control, and complications after salvage local therapy for postradiation prostate-specific antigen failure: a systematic review of the literature. Cancer. 2007;110(7):1417–28.

    Article  PubMed  Google Scholar 

  64. Pound CR, et al. Natural history of progression after PSA elevation following radical prostatectomy. JAMA. 1999;281(17):1591–7.

    Article  CAS  PubMed  Google Scholar 

  65. •• Andriole GL, et al. The impact of positron emission tomography with (18)F-fluciclovine on the management of patients with biochemical recurrence of prostate cancer: results from the LOCATE trial. J Urol. 2018;201(2):322–31. The LOCATE study results describe a significant change in management in patients with biochemical recurrent prostate cancer.

  66. Calais J, Cao M, Nickols NG. The utility of PET/CT in the planning of external radiation therapy for prostate cancer. J Nucl Med. 2018;59(4):557–67.

    Article  CAS  PubMed  Google Scholar 

  67. Jani AB, et al. Impact of (18)F-fluciclovine PET on target volume definition for postprostatectomy salvage radiotherapy: initial findings from a randomized trial. J Nucl Med. 2017;58(3):412–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Gandaglia G, et al. Short- and long-term outcomes of salvage lymph node dissection in patients with clinically recurrent prostate cancer. Eur Urol. 2017;35(6):255.

    Google Scholar 

  69. Zattoni F, et al. Mid-term outcomes following salvage lymph node dissection for prostate cancer nodal recurrence status post-radical prostatectomy. Eur Urol Focus. 2016;2(5):522–31.

    Article  PubMed  Google Scholar 

  70. Torricelli FCM, et al. Robotic salvage lymph node dissection after radical prostatectomy. Int Braz J Urol. 2015;41(4):819–20.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Karnes RJ, et al. Salvage lymph node dissection for prostate cancer nodal recurrence detected by 11C-choline positron emission tomography/computerized tomography. J Urol. 2015;193(1):111–6.

    Article  PubMed  Google Scholar 

  72. Linxweiler J, et al. Robotic salvage lymph node dissection in prostate cancer after PSMA- or Choline-PET/CT: operative and early oncological results. Eur Urol Suppl. 2018;17(2):e577–8.

    Article  Google Scholar 

  73. Ceci F, et al. Evaluation of prostate cancer with 11C-Choline PET/CT for treatment planning, response assessment, and prognosis. J Nucl Med. 2016;57(Supplement_3):49S–54S.

    Article  CAS  PubMed  Google Scholar 

  74. Lenzo NP, Meyrick D, Turner JH. Review of gallium-68 PSMA PET/CT imaging in the management of prostate cancer. Diagnostics (Basel). 2018;8(1):16.

    Article  PubMed Central  CAS  Google Scholar 

  75. •• Calais J, et al. Comparison of (68)Ga-PSMA-11 and (18)F-fluciclovine PET/CT in a case series of 10 patients with prostate cancer recurrence. J Nucl Med. 2018;59(5):789–94. Preliminary evidence that 68Ga-PSMA-11 PET/CT scan may have a better detection rate compared to fluciclovine PET/CT scan.

  76. Bravaccini S, et al. PSMA expression: a potential ally for the pathologist in prostate cancer diagnosis. Sci Rep. 2018;8(1):4254.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Emmett L, et al. Lutetium (177) PSMA radionuclide therapy for men with prostate cancer: a review of the current literature and discussion of practical aspects of therapy. J Med Radiat Sci. 2017;64(1):52–60.

    Article  PubMed  PubMed Central  Google Scholar 

  78. Evans MJ, et al. Noninvasive measurement of androgen receptor signaling with a positron-emitting radiopharmaceutical that targets prostate-specific membrane antigen. Proc Natl Acad Sci USA. 2011;108(23):9578–82.

    Article  CAS  PubMed  Google Scholar 

  79. Meller B, et al. Alterations in androgen deprivation enhanced prostate-specific membrane antigen (PSMA) expression in prostate cancer cells as a target for diagnostics and therapy. EJNMMI Res. 2015;5(1):66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Afshar-Oromieh A, et al. Impact of long-term androgen deprivation therapy on PSMA ligand PET/CT in patients with castration-sensitive prostate cancer. Eur J Nucl Med Mol Imaging. 2018;45(12):2045–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Audet-Walsh E, et al. Nuclear mTOR acts as a transcriptional integrator of the androgen signaling pathway in prostate cancer. Genes Dev. 2017;31(12):1228–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Correspondence to Bital Savir-Baruch.

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Bital Savir-Baruch: Grant sponsored by Blue Earth Diagnostics; Philip, Lecturer. The other authors declare that they have no conflict of interest.

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Savir-Baruch, B., Tade, F., Henry, E. et al. Emerging Role of Fluciclovine and Other Next Generation PET Imaging Agents in Prostate Cancer Management. Curr Radiol Rep 7, 16 (2019). https://doi.org/10.1007/s40134-019-0328-6

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